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Sleep Disturbances Linked to Alzheimer’s Risk

July 10, 2017 -- Here’s another reason to get a good night’s sleep: Interrupting a deep phase of sleep appears to cause more of the proteins associated with Alzheimer’s disease to collect in your brain, a new study from researchers at Washington University concludes.

The findings, published Monday in the research journal Brain, suggest that even a short-term disruption could lead to higher levels of beta amyloid, a protein that forms plaques associated with Alzheimer’s. Longer stretches may also lead to higher levels of another protein known as tau, which forms tangles that can damage brain cells, the researchers report.

Brain cells release fewer amyloid proteins during good sleep, and a growing body of research points toward a relationship between poor sleep and Alzheimer’s. But doctors and scientists are still trying to understand that connection, and the new study marks the first time researchers have linked problems with a specific phase of sleep to more amyloid proteins, says Yo-El Ju, MD, a neurologist and sleep medicine doctor at Washington University.

“Certainly, it seems like people who have poor sleep or sleep disorders are at higher risk of Alzheimer’s disease,” Ju says. “But also, the brain changes of Alzheimer’s disease seem to worsen sleep.”

More Disturbances, More Amyloid

Ju and her colleagues set out to identify how sleep disturbances could lead to a higher long-term risk of Alzheimer’s, and identify which part of sleep was most related to lower levels of beta amyloid.

The researchers wrote a computer program designed to disrupt slow-wave sleep -- a deep, dreamless, refreshing slumber -- in a group of 17 volunteers, then measured their levels of beta amyloid. They gave the patients earphones to wear as they fell asleep in a controlled environment. A computer followed a readout of the brainwaves of the sleeping people. Once they fell into slow-wave sleep, the computer beeped at half of them, growing louder until the participants were knocked out of that restful phase.

“Our goal was not to wake them up,” Ju says. “We wanted them to continue to sleep, just in lighter stages of sleep.”

Researchers repeated the experiment about a month later but switched the groups. After each night, doctors gave the participants, who ranged from 35 to 65, a spinal tap to collect samples of their cerebrospinal fluid, which surrounds the brain. Tests on those samples showed nine participants had higher levels of beta amyloid after sleep disruptions, and the increases were greater in those whose sleep was more disturbed.

“When we did not let their brain cells rest by giving them all those beeps, then they continued to produce as much amyloid as in lighter sleep or wakefulness,” Ju says.

In addition, participants wore devices on their wrists to help measure their sleep at home during the days before the procedure. People whose devices pointed to worse sleep had higher levels of tau proteins, the study reports.  

“These were normal, healthy, young or middle-aged people,” Ju says. “They have no sleep disorders. Even in this very healthy population, we see variations in their sleep at home that does affect tau and amyloid levels.”

'Impressive' Findings

Alzheimer’s is a brain disease that gets worse over time. It robs people of their memories and mental abilities. Although beta amyloid and tau are associated with the disease, not everyone who has these proteins in their brain gets Alzheimer’s.

More than 5 million people are now battling the illness in the United States, and it has become the sixth-leading cause of death. The cost of caring for Alzheimer’s patients is expected to top $250 billion this year.

Previous studies in animals have pointed toward a link between slow-wave sleep and higher amyloid levels, says Adam Spira, PhD, a clinical psychologist who studies sleep, aging, and Alzheimer’s at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

The new study shows the same sort of results in humans, but more studies are needed to figure out the mechanism behind those results, he says.

“It’ll be interesting to see whether disruption of other specific sleep stages leads to smaller increases or no increases,” Spira says.

The new study includes “several impressive findings,” says Miranda Lim, MD, PhD, who studies sleep and neurological disorders at Oregon Health & Science University.

Most studies have looked only at associations between Alzheimer’s and sleep, but the experiment by Ju and her colleagues tested how one specific stage of sleep affected amyloid levels, says Lim, who was not involved with the study.

“Sleep research is at the forefront of our understanding of the pathology, progression, and potential therapeutic approaches to Alzheimer's disease right now,” she says. “As sleep is a fundamental biological process that varies over the lifespan of the individual, understanding how sleep modulates toxic buildup of proteins relevant to neurological diseases will be instrumental to implementing future therapies, for both the directly sleep-related therapies as well as in enhancing other drug targets.”

An "exciting and obvious” follow-up could be to try to improve slow-wave sleep and measure the effect on tau and amyloid levels, she adds, which could point toward a potential treatment.


WebMD Health News Reviewed by Michael W. Smith, MD


Brain: “Slow wave sleep disruption increases cerebrospinal fluid amyloid-B levels.”

Yo-El Ju MD, Washington University, St. Louis.

Neurodegenerative Disease Management: “The sleep-wake cycle and Alzheimer's disease: what do we know?”

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